Use of 5-[76Br]bromo-2′-fIuoro-2′-deoxyuridine as a ligand for tumour proliferation:: validation in an animal tumour model

被引:30
作者
Borbath, I
Grégoire, V
Bergström, M
Laryea, D
Långström, B
Pauwels, S
机构
[1] Catholic Univ Louvain, Dept Radiat Oncol, Brussels, Belgium
[2] Catholic Univ Louvain, Dept Nucl Med, Brussels, Belgium
[3] Uppsala Univ, PET Ctr, Uppsala, Sweden
关键词
tumour proliferation; PET; thymidine; bromodeoxyuridine; animal model;
D O I
10.1007/s00259-001-0689-x
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Uncontrolled cell proliferation is one of the prominent features in cancer development. Precise tools are needed for determination of the proliferation rate before, during and after treatment, thereby permitting assessment of treatment efficacy. The purpose of this study was to validate the use of 5-[Br-76]bromo-2'-fluoro-2'-deoxyuridine (Br-76-BFU) as a proliferation marker in an animal tumour model. Comparison was made with 2-[C-14]thymidine (C-14-TdR) incorporation and the labelling index assessed by bromodeoxyuridine (BrdUrd-LI). Fibrosarcoma (NFSA)-bearing mice were used for all experiments. Gemcitabine (dFdC), a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. dFdC was injected intraperitoneally at a dose of 0.5 mg/kg or 40 mg/kg to induce partial (approximate to50%) or complete inhibition of DNA synthesis, respectively. Br-76-BFU (0.5-3 MBq per animal), C-14-TdR (37-74 kBq per animal) and cold BrdUrd (60 mg/kg) were injected intraperitoneally in combination or alone. Animals were sacrificed at various times after tracer administration, and tumour and small intestine were removed for determination of radioactivity in whole tissue and the DNA fraction, as well as for LI assessment by flow cytometry. Cimetidine (6 mg/kg) was used to decrease Br-76-BFU elimination and increase its bioavailability. The fraction of radioactivity associated with DNA increased with the time interval between tracer injection and tissue removal. At 6 h after injection, for both tracers, more than 95% of the radioactivity in the tumours was associated with the DNA fraction and an excellent correlation was observed with the LI. Similar findings were observed in the small intestine. Under all experimental conditions, Br-76-BFU uptake was 4-10 times lower than C-14-TdR uptake. Co-injection of cimetidine resulted in a three- to fourfold increase in Br-76-BFU incorporation without affecting the effect of dFdC on DNA synthesis. Br-76-BFU is a potentially good tracer for the assessment of tumour proliferation. It has all the specifications required of a PET tracer for clinical use. One limitation to its use is the necessity of co-injecting cimetidine to increase its bioavailability and hence its sensitivity for PET detection.
引用
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页码:19 / 27
页数:9
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